Anti-pathogenicity of Acanthus ilicifolius leaf extracts against A. hydrophila infection in Labeo rohita fingerlings.

Antibiotic resistance has become one of the inevitable barrier in aquaculture disease management. Herbal drugs has evolved to be the novel ways of combating drug resistant pathogens. In the current investigation, leaf extracts of mangrove plant, Acanthus ilicifolius were assessed for in vitro studies, among the selected four extracts, methanol extract has expressed highest antibacterial activity against P .aeruginosa (4 ± 0.3 mm), A. hydrophila (5.9 ± 0.5 mm), S. aureus (3.5 ± 0.7 mm) and B. subtilis (2.9 ± 0.5 mm) and antioxidant activity, DPPH (81.3 ± 1.0 AAEµg/ml) and FRAP (139.1 ± 1.5 AAEµg/ml).TPC and TFC were higher in the methanolic extract and has exhibited positive correlation with both DPPH and FRAP assays. Considering the in vitro efficiency, methanol extract was purified successively by column and thin layer chromatography and characterisation by GC-MS unveiled the presence of 2-Propanethiol, Trimethylphosphine, Pentanoyl chloride, Dimethylhydroxymethylphosphine and Propanedinitrile, ethylidene. A. hydrophila infected L. rohita fingerlings has survival percentage 81% and 94% in extract treated groups over 0% in negative control and 71% in positive control.

Vidutolimod in Combination With Atezolizumab With and Without Radiation Therapy in Patients With Programmed Cell Death Protein 1 or Programmed Death-Ligand 1 Blockade-Resistant Advanced NSCLC.

Introduction: Vidutolimod, a CpG-A TLR9 agonist, was investigated in a phase 1b study (CMP-001-003; ClinicalTrials.gov, NCT03438318) in combination with atezolizumab with and without radiation therapy (RT) in patients with advanced NSCLC. Methods: Patients with progressive disease after anti-programmed cell death protein 1 or programmed death-ligand 1 therapy received either vidutolimod and atezolizumab (part A) or vidutolimod, atezolizumab, and RT (part B). The primary objective was to evaluate the safety of vidutolimod and atezolizumab with and without RT. Key secondary end point was best objective response rate per Response Evaluation Criteria in Solid Tumors, version 1.1. Results: Between March 28, 2018, and July 25, 2019, a total of 29 patients were enrolled and received at least one dose of vidutolimod (part A, n = 13; part B, n = 16). Intratumoral injections of vidutolimod were administered successfully, including injection of visceral lesions. The most common treatment-related adverse events (≥30%) were flu-like symptoms and hypotension. No objective responses were observed; 23.1% and 50.0% of the patients in parts A and B, respectively, had stable disease as best response. In parts A and B, 15.4% and 25.0% of the patients, respectively, had tumor shrinkage (<30% decrease in tumor size, nonirradiated). Enrollment was stopped owing to lack of objective responses. In the two patients with initial tumor shrinkage in part A, a strong serum induction of C-X-C motif chemokine ligand 10 was observed. Conclusions: Vidutolimod and atezolizumab with and without RT had a manageable safety profile, with minimal clinical activity in heavily pretreated patients with programmed cell death protein 1 or programmed death-ligand 1 blockade-resistant NSCLC.

The Use of Intravenous Lidocaine as an Analgesic Modality in the Austere Environment: Two Cases.

Providing effective analgesia for trauma in austere settings is particularly difficult and often complicated by equipment and medication limitations and harsh environmental conditions. Common modalities that are employed in conventional clinical practices may not be available or pragmatic in austere environments. Furthermore, side effects such as sedation, altered mentation, or hypoxemia require additional resources and attention. We report 2 cases that demonstrate the use of intravenous lidocaine for the management of acute pain, secondary to trauma, in an austere environment. In the first, the administration of intravenous lidocaine reduced pain, secondary to a tibia fracture, thereby facilitating splinting. In the second, a patient, who had sustained rib fractures, was also treated with intravenous lidocaine. In this case, the analgesic effects of the medication resulted in reduction in pain and improvement in pulmonary function. Of note, the narrow therapeutic window of this modality was made evident as both patients transiently experienced tinnitus following the initial lidocaine bolus. This report describes 2 cases in which intravenous lidocaine was used to manage acute pain, in an austere environment, while avoiding many of the detrimental effects that accompany alternative analgesics.

Uroflowmetric analysis and derivation of nomograms for normal paediatric Indian population between 5 to 15 years of age.

Objective: We aimed to established normal uroflowmetric values and subsequently derived nomograms of maximum flow rate (Qmax) and average flow rate (Qavg) against voided volume (VV) in children aged 5-15 years at our institute. Methods: A total of 440 children underwent uroflowmetric evaluation with no history of urological, renal, psychiatric, or neurological disorder between 5 and 15 years of age. Each subject data regarding Qmax, Qavg, VV, time to Qmax, and flow time, as well as age, sex, height, and weight were recorded. Of the 440 children, around 300 (68.18%) children could produce a normal flow rate at VV of more than 50 mL. Of the remaining 140 (31.82%) children, 50.00% voided less than 50 mL, and remaining 50.00% had abnormal voiding pattern, staccato or interrupted (21.43% each) and plateau or tower shaped (3.57% each). Cases were divided into two age groups (5-9 years and 10-15 years), and uroflowmetric analysis was done between boys and girls in both age groups to derive nomograms of Qavg and Qmax. Results: Qmax and Qavg flow nomograms were plotted for boys and girls. Mean Qmax for boys was 16.68 mL/s and for girls 20.69 mL/s. The mean Qavg values were 11.04 mL/s and 8.60 mL/s for girls and boys, respectively. The Qmax and Qavg values were higher in girls. There were significant increases in flow rates with increasing age, body surface area, and VV in both sexes. Conclusions: Nomograms for Qmax and Qavg may be a useful tool in evaluation of lower urinary tract disturbances in children.

A Rare Case Report of Primary Hydatid Disease of the Scapula - an Unforeseen Diagnosis!

Introduction: Hydatid disease of the bone is a parasitic infestation in the form of cystic echinococcosis by a tapeworm echinococcus granulosus. Its manifestation in the bone is relatively low and has the ability to mimic other skeletal pathologies. Case Report: We came across a 30-year-old male farmer with complaints of sero-purulent discharge from a sinus tract wound in the axilla for the past 3 years. He had been previously evaluated elsewhere with blood investigations, pus culture/sensitivity tests, MRI, and CT scans. Blood reports and culture/sensitivity tests were inconclusive and imaging tests were suggestive of a sinus tract originating from the right scapula. He was incorrectly diagnosed as a case of Tuberculosis of the Scapula and started on anti-tubercular medications for 9 months which was ineffective. To confirm the diagnosis, a biopsy was taken from the scapular lesion through a posterior approach. Histological tests revealed a cystic lesion composed of trilaminar membrane consisting of dead and degenerating scolices consistent with "Hydatid Cyst of Bone." Conclusion: Hydatid disease of the bone has an inconsistent clinical picture which makes diagnosing this rare disease even more difficult. A high suspicion for hydatid infestation in bone pathologies could help in diagnosing the disease at the earliest.

Biodegradation of plastic polymers by fungi: a brief review.

Plastic polymers are non-degradable solid wastes that have become a great threat to the whole world and degradation of these plastics would take a few decades. Compared with other degradation processes, the biodegradation process is the most effective and best way for plastic degradation due to its non-polluting mechanism, eco-friendly nature, and cost-effectiveness. Biodegradation of synthetic plastics is a very slow process that also involves environmental factors and the action of wild microbial species. In this plastic biodegradation, fungi play a pivotal role, it acts on plastics by secreting some degrading enzymes, i.e., cutinase`, lipase, and proteases, lignocellulolytic enzymes, and also the presence of some pro-oxidant ions can cause effective degradation. The oxidation or hydrolysis by the enzyme creates functional groups that improve the hydrophilicity of polymers, and consequently degrade the high molecular weight polymer into low molecular weight. This leads to the degradation of plastics within a few days. Some well-known species which show effective degradation on plastics are Aspergillus nidulans, Aspergillus flavus, Aspergillus glaucus, Aspergillus oryzae, Aspergillus nomius, Penicillium griseofulvum, Bjerkandera adusta, Phanerochaete chrysosporium, Cladosporium cladosporioides, etc., and some other saprotrophic fungi, such as Pleurotus abalones, Pleurotus ostreatus, Agaricus bisporus and Pleurotus eryngii which also helps in degradation of plastics by growing on them. Some studies say that the degradation of plastics was more effective when photodegradation and thermo-oxidative mechanisms involved with the biodegradation simultaneously can make the degradation faster and easier. This present review gives current knowledge regarding different species of fungi that are involved in the degradation of plastics by their different enzymatic mechanisms to degrade different forms of plastic polymers.

Identification of candida albicans and nonalbicans candida resistant species in tobacco users and oral squamous cell carcinoma patients: Comparison of HiCrome agar and automated VITEK 2 system.

Introduction: Candida is most common fungal pathogen in the immunocompromised and medically ill patients. Higher prevalence of Candida albicans has been reported in tobacco users and oral squamous cell carcinoma (OSCC) patients which may be due to immunosuppression. Recently, emergence of nonalbicans candida (NAC) species resistant to conventional antifungal treatment has been observed that requires accurate identification of organisms at species level for reduction of progression of suspicious oral lesions toward malignancy. Aims and Objectives: To detect and compare the prevalence of C. albicans and NAC species smokeless tobacco chewers, histopathologically confirmed oral squamous cell carcinoma patients and the normal individuals. Effectiveness of automated Vitek 2 system in comparison to HiCrome agar color media in the identification of the candida species was also evaluated. Methodology: One hundred and fifty patients (90 males, 60 females) aged between 20 and 76 years were divided into three groups: Group I individuals with habit of chewing Gutka, and betel quid/pan masala with or without tobacco, Group II individuals with clinically and histopathologically confirmed oral squamous cell carcinoma and Group III comprised of controls. Salivary samples were cultured on HiCrome agar color media and results were compared with those of Vitek 2 system in the accurate identification of candida species. Data were statistically analyzed and Chi-square test was used to estimate the effectiveness of color and Vitek method in the identification of candida species in all the three groups. P < 0.05 was considered to be statistically significant. RESULTS: HiCrome agar color method identified six candida isolates C. albicans, Candida tropicalis, Candida krusei and Candida glabrata isolates in all the three groups, with 0.00 unidentified organisms (P = 0.00001) whereas VITEK 2 system identified five isolates of candida; C. albicans, Candida famat, Candida ciferri, Candida gulleri, C. tropicalis, unidentified organisms were observed in 26% of subjects. Further confirmation by supplemental tests indicated the presence of two or three organisms of different species/or subspecies with low reactivity biopattern. Higher incidence of opportunistic infections was seen in Group II OSCC patients (P = 0.00001). Conclusion: The results suggested that there is shift toward NAC species, with higher species diversity in OSCC patients followed by gutka, betel quid/pan masala with or without tobacco users. Conventional agar media culture methods of species identification should be used in conjunction with automated Vitek 2 method for better control of candida-associated oral cancer.

Metabolic labeling and targeted modulation of dendritic cells.

Targeted immunomodulation of dendritic cells (DCs) in vivo will enable manipulation of T-cell priming and amplification of anticancer immune responses, but a general strategy has been lacking. Here we show that DCs concentrated by a biomaterial can be metabolically labelled with azido groups in situ, which allows for their subsequent tracking and targeted modulation over time. Azido-labelled DCs were detected in lymph nodes for weeks, and could covalently capture dibenzocyclooctyne (DBCO)-bearing antigens and adjuvants via efficient Click chemistry for improved antigen-specific CD8+ T-cell responses and antitumour efficacy. We also show that azido labelling of DCs allowed for in vitro and in vivo conjugation of DBCO-modified cytokines, including DBCO-IL-15/IL-15Rα, to improve priming of antigen-specific CD8+ T cells. This DC labelling and targeted modulation technology provides an unprecedented strategy for manipulating DCs and regulating DC-T-cell interactions in vivo.

Application of the Joint Trauma System Clinical Practice Guideline for Pain, Anxiety, and Delirium in a Combat Support Hospital in Iraq.

INTRODUCTION: The 2017 Joint Trauma System Clinical Practice Guideline for Pain, Anxiety, and Delirium (JTS CPG) provides an evidence-based framework for managing pain, anxiety, and delirium in combat settings. In this study, we evaluate the use of multimodal analgesia and assess pain outcomes, as indicated by the JTS CPG, at the combat support hospital (CSH). MATERIALS AND METHODS: In this quality improvement project, data were collected for all patients, presenting to the CSH in Baghdad, Iraq, who received consultation from the acute pain service from October 10, 2017 to February 27, 2018. Univariate analyses described patient demographic and clinical characteristics. Defense and Veterans Pain Rating Scale (DVPRS) scores, physical therapy completion, and sleep duration were recorded for each patient daily. Correlations assessed relationships between variables, including clinical characteristics and DVPRS scores. RESULTS: 34 patients were included in this study. About 65% of the patients included in this study were Iraqi military, while the other 35% were U.S. or Coalition Forces. Over half received more than one class of analgesic medication. The majority of patients received regional anesthesia, with 17 different techniques utilized. The DVPRS had acceptable internal consistency (Cronbach alpha = 0.87, 95% CI 0.80, 0.95). There was a significant difference in median DVPRS pain intensity scores between those who met physical therapy goals and those who did not. Sleep duration was negatively correlated with both the DVPRS pain intensity and sleep scores. CONCLUSIONS: This report indicates that acute pain service teams integrated in a CSH can feasibly implement JTS CPGs using a team-based approach. Given the military's emphasis on managing complex pain and disability among survivors beginning in the combat environment, it is imperative that innovations and best practices, like the JTS CPG, be assessed in the combat setting.

Feasibility of Hepatology-Directed Microwave Ablation in Management of Hepatocellular Carcinoma in North America: A Pilot Project.

In North America, the role of Hepatologists in treatment of hepatocellular carcinoma is limited. We conducted a pilot project wherein a Hepatologist participated directly in microwave ablation of HCC at an academic center in the United States (n = 14). The pilot project shows promising outcomes, with complete remission rate of 93%.

Anti-tumor immunity induced by ectopic expression of viral antigens is transient and limited by immune escape.

Immunotherapeutic treatments in head and neck cancer clinical trials include cancer vaccines targeting foreign viral antigens or mutational neoantigens derived from cancer-expressed proteins. Anti-tumor immune responses place cancer cells under selective pressure to lose or downregulate target antigens; therefore, vaccination against virus- or host- "driver" oncogenes are proposed as a strategy to overcome immune escape. Herein, we demonstrate the impact of immunogenic viral antigens on anti-tumor response and immune editing in MOC2-E6E7, a syngeneic murine oral cancer cell line expressing HPV-16 E6 and E7 oncoproteins. Using orthotopic syngeneic models, we observed in vivo tumor growth kinetics of MOC2-E6E7 is delayed in immunocompetent mice compared to parental MOC2 tumors. In contrast, tumor growth remained similar in Rag1-/- mice lacking adaptive immunity. MOC2-E6E7 tumors demonstrated an "inflamed" or immune-activated tumor microenvironment and greater infiltration of CD8+ T cells compared to MOC2. By real-time PCR, we detected downregulation of E6 and E7 genes in MOC2-E6E7 tumors only in immunocompetent mice, suggesting the loss of ectopic viral antigen expression due to immune editing. We then assessed the efficacy of a biomaterials-based mesoporous silica rod (MSR) cancer vaccine targeting HPV-16 E7 in our model. Vaccination induced robust infiltration of antigen-specific CD8+ T cells, which led to tumor growth delay and modestly prolonged survival in MOC2-E6E7 tumors. Increased efficacy was seen in a separate head and neck cancer tumor model, mEER, which obligately expresses E7 antigen. Collectively, our data highlight the need for both immunogenicity and 'driver' status of target antigens to be considered in cancer vaccine design.

Regional Anesthesia in the Combat Setting: Are ACGME Requirements Enough?

INTRODUCTION: Updated Joint Trauma System Clinical Practice Guidelines (CPG) indicate regional anesthesia and pain management (RAAPM) are important for combat casualty care. However, it is unclear whether military anesthesiology residents are receiving adequate RAAPM training to meet the CPGs. The goal of this study was to conduct a preliminary evaluation of resident-completed combat-relevant regional anesthesia procedures. It was hypothesized that most residents would perform an adequate number of each procedure to presume proficiency. MATERIALS AND METHODS: Resident-performed, combat-relevant regional anesthesia procedure frequency was extracted from a database maintained at a military anesthesiology residency program. Data collection was limited to a 1-year period. Univariate statistics described procedure distributions, frequencies, and proportion of residents achieving pre-defined, empirically-supported experience criteria for each technique. Analyses examined proportional differences in meeting experience criteria by training-year. RESULTS: Residents (N = 41) performed a variety of procedures. Simple procedures, such as saphenous peripheral nerve blocks, were performed at a greater frequency than more complicated procedures such as thoracic epidurals, continuous peripheral nerve blocks, and transverse abdominus plane blocks. The majority of residents met experience criteria for four out of the eight measured combat-relevant blocks. There were no proportional differences in meeting procedural experience criteria across the different training levels. CONCLUSIONS: These results suggest a possible gap between the needs of the Military Health System during conflict and current residency training experiences. Reasons for this gap, as well as solutions, are explored.

LAST Double Check - A Comprehensive Pre-Regional Checklist for the Busy Institution.

INTRODUCTION: Wrong site peripheral nerve blocks are included in the National Quality Forum and Joint Commission's category of "never event." Multiple attempts have been made by various groups in an effort to eliminate these events. Prior attempts to eliminate these never events include the Regional Block Preprocedural Checklist provided by the American Society of Regional Anesthesia (ASRA) taskforce. Following a series of errors involving anticoagulation prior to regional anesthesia, our department saw a need for a more comprehensive checklist. MATERIALS AND METHODS: An expert panel developed the LAST Double Check Checklist with the aim of identifying and eliminating errors associated with regional anesthesia delivery. This checklist was implemented over the course of two 30 d trial periods. Feedback was collected and any delays associated with implementation were recorded. RESULTS: There were no reported procedures performed on patients taking anticoagulation or reported case delays during the two 30 d trials. A total of 350 regional anesthetics were performed during both trials. During the first week of implementation, a patient was identified as having received enoxaparin, despite the electronic medical record showing the medication as held. The planned regional anesthetic was not performed given increased risk of bleeding. Feedback collected during the trial periods was incorporated into the final draft and implementation of the LAST Double Check for use in all locations where regional anesthesia is performed. There have been no post-implementation events reported (11-mo period, greater than 1,000 regional anesthetics performed). CONCLUSION: The LAST Double Check is a more comprehensive checklist with the aim of preventing errors associated with wrong site blocks, anticoagulation administration, and care team coordination. This checklist covers areas of the patient history that are routinely reviewed prior to regional anesthesia administration and did not contribute to delay in arrival to the operating room.

Hepatitis C virus knowledge improves hepatitis C virus screening practices among primary care physicians.

AIM: To understand the role of knowledge as a promoter of hepatitis C virus (HCV) screening among primary care physicians (PCP). METHODS: A 45-item online questionnaire assessing knowledge of HCV natural history, risk factors, and treatment was distributed to 163 PCP. Logistic regression, adjusted for survey responses, assessed associations between PCP knowledge of HCV natural history and treatment and birth cohort (i.e., birth between 1945 and 1965) screening. Response stratification and weighting were used to account for nonresponse and to permit extension of responses to the entire survey population. Associations between various predictors including demographic characteristics, level of training, and HCV treatment experience and HCV knowledge were assessed. RESULTS: Ninety-one individuals (55.8%) responded. Abnormal liver enzymes (49.4%), assessment of HCV-related risk factors (30.6%), and birth cohort membership (20%) were the leading HCV screening indications. Most PCP (64.7%) felt that the combination of risk-factor and birth cohort screening utilizing a self-administered survey while awaiting the physician (55.3%) were the most efficient screening practices. Implementation of birth cohort screening was associated with awareness of the recommendations (P-value = 0.01), knowledge of HCV natural history (P-value < 0.01), and prior management of HCV patients (P-value < 0.01). PCP with knowledge of HCV treatment was also knowledgeable about HCV natural history (P-value < 0.01). Similarly, awareness of age-based screening recommendations was associated with HCV treatment knowledge (P-value = 0.03). CONCLUSION: Comprehensive knowledge of HCV is critical to motivate HCV screening. PCP-targeted educational interventions are required to expand the HCV workforce and linkage-to-care opportunities as we seek global HCV eradication.

Novel prodrug PRX-P4-003, selectively activated by gut enzymes, may reduce the risk of iatrogenic addiction and abuse.

OBJECTIVES: Prescription stimulants are vulnerable to oral and parenteral abuse. Intravenous forms of abuse may be most detrimental due to an enhanced risk of dependence, overdose, and infectious diseases. Our objective was to discover an orally active prodrug of a stimulant that would not be easily converted to its parent when injected, thus hindering intravenous abuse. METHODS: Following an initial analysis of stimulant structures, the fencamfamine isomer [(-)-FCF; (N-ethyl-3-phenylbicyclo[2.2.1]heptan-2-amine)] was chosen as a parent drug due to its favorable biochemical properties. Subsequently, PRX-P4-003 {(-)-N-(Octadecanoyloxymethoxycarbonyl)-N-ethyl-3-phenylbicyclo[2.2.1]heptan-2-amine} qualified for further development. Experimental testing of PRX-P4-003 included radioligand binding assays, stability studies, and rodent pharmacokinetic and locomotor assays. RESULTS: Prodrug PRX-P4-003 is a pharmacologically inactive, hydrophobic compound, whereas its parent (-)-FCF is a dopamine reuptake inhibitor with weaker effects on norepinephrine reuptake (Ki = 0.07 and 0.80 µM, respectively). PRX-P4-003 is metabolized to (-)-FCF in simulated intestinal fluid (with pancreatin) but not in simulated gastric fluid (with pepsin). Finally, PRX-P4-003 shows a significant oral but no intravenous increase in locomotion, correlating with its pharmacokinetics by these different routes of administration. CONCLUSIONS: PRX-P4-003 is a novel prodrug stimulant enzymatically activated in the gut. Our data suggest a pancreatic, lipase-based mechanism of activation and as only 1% of this enzyme is found in the systemic circulation, PRX-P4-003 is unlikely to be bioactive if injected intravenously. Enzymatic release of (-)-FCF is needed prior to its systemic absorption, which may discourage oral abuse (e.g., by chewing). PRX-P4-003 is being developed for apathy in Alzheimer's disease and binge eating disorder.

Injectable, Tough Alginate Cryogels as Cancer Vaccines.

A covalently crosslinked methacrylated (MA)-alginate cryogel vaccine has been previously shown to generate a potent response against murine melanoma, but is not mechanically robust and requires a large 16G needle for delivery. Here, covalent and ionic crosslinking of cryogels are combined with the hypothesis that this will result in a tough MA-alginate cryogel with improved injectability. All tough cryogels can be injected through a smaller, 18G needle without sustaining any damage, while covalently crosslinked-only cryogels break after injection. Cytosine-phosphodiester-guanine (CpG)-delivering tough cryogels effectively activate dendritic cells (DCs). Granulocyte macrophage colony-stimulating factor releasing tough cryogels recruit four times more DCs than blank gels by day 7 in vivo. The tough cryogel vaccine induces strong antigen-specific cytotoxic T-lymphocyte and humoral responses. These vaccines prevent tumor formation in 80% of mice inoculated with HER2/neu-overexpressing DD breast cancer cells. The MA-alginate tough cryogels provide a promising minimally invasive delivery platform for cancer vaccinations.

Scaffolds that mimic antigen-presenting cells enable ex vivo expansion of primary T cells.

Therapeutic ex vivo T-cell expansion is limited by low rates and T-cell products of limited functionality. Here we describe a system that mimics natural antigen-presenting cells (APCs) and consists of a fluid lipid bilayer supported by mesoporous silica micro-rods. The lipid bilayer presents membrane-bound cues for T-cell receptor stimulation and costimulation, while the micro-rods enable sustained release of soluble paracrine cues. Using anti-CD3, anti-CD28, and interleukin-2, we show that the APC-mimetic scaffolds (APC-ms) promote two- to tenfold greater polyclonal expansion of primary mouse and human T cells compared with commercial expansion beads (Dynabeads). The efficiency of expansion depends on the density of stimulatory cues and the amount of material in the starting culture. Following a single stimulation, APC-ms enables antigen-specific expansion of rare cytotoxic T-cell subpopulations at a greater magnitude than autologous monocyte-derived dendritic cells after 2 weeks. APC-ms support over fivefold greater expansion of restimulated CD19 CAR-T cells than Dynabeads, with similar efficacy in a xenograft lymphoma model.